Read by QxMD icon Read


Uwe Wolfrum, Kerstin Nagel-Wolfrum
The human Usher syndrome (USH) is a complex, rare disease manifesting in its most common form of inherited deaf-blindness. Due to the heterogeneous manifestation of the clinical symptoms, three clinical types (USH1-3) are distinguished according to the severity of the disease pattern. For a correct diagnosis, in addition to the auditory tests in early newborn screening, ophthalmological examinations and molecular genetic analysis are important. Ten known USH genes encode proteins, which are from heterogeneous protein families, interact in functional protein networks...
March 2018: Klinische Monatsblätter Für Augenheilkunde
Christina Gerth-Kahlert, Samuel Koller
Ciliopathies are disorders caused by ciliary dysfunction and can affect an organ system or tissues. Isolated or syndromic retinal dystrophies are the most common ocular manifestation of ciliopathies. The photoreceptor connecting cilium plays a leading role in these ciliopathy-related retinal dystrophies. Dysfunctional photoreceptor cilia cause the most severe type of retinal dystrophy: Leber's congenital amaurosis (LCA). The most common syndromic ciliopathies with an ocular manifestation are Bardet-Biedl syndrome (BBS) and Usher syndrome...
March 2018: Klinische Monatsblätter Für Augenheilkunde
Wen-Li Deng, Mei-Ling Gao, Xin-Lan Lei, Ji-Neng Lv, Huan Zhao, Kai-Wen He, Xi-Xi Xia, Ling-Yun Li, Yu-Chen Chen, Yan-Ping Li, Deng Pan, Tian Xue, Zi-Bing Jin
Retinitis pigmentosa (RP) is an irreversible, inherited retinopathy in which early-onset nyctalopia is observed. Despite the genetic heterogeneity of RP, RPGR mutations are the most common causes of this disease. Here, we generated induced pluripotent stem cells (iPSCs) from three RP patients with different frameshift mutations in the RPGR gene, which were then differentiated into retinal pigment epithelium (RPE) cells and well-structured retinal organoids possessing electrophysiological properties. We observed significant defects in photoreceptor in terms of morphology, localization, transcriptional profiling, and electrophysiological activity...
February 28, 2018: Stem Cell Reports
Sorina Danescu, Cristina Has, Corina Baican, Thomas Müller, Adrian Baican
We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with incontinentia pigmenti. The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. We cannot establish a link between incontinentia pigmenti, a very rare disease, and hepatic ciliopathy, but we suggest that hepatic evaluation should be considered in patients with incontinentia pigmenti.
March 8, 2018: Australasian Journal of Dermatology
Maria D Garcia, Camila V Ventura, João R Dias, Ta Chen P Chang, Audina M Berrocal
Purpose: We present the first case in the literature of a patient with Kartagener syndrome and ocular findings of nonexudative age-related macular degeneration. Observations: A 55-year-old woman with Kartagener syndrome and chronic angle closure glaucoma presented for evaluation of the retina. Optos ultra-widefield imaging of the fundus showed glaucomatous cupping, drusen, and retinal pigment epithelium changes within the macular region. Humphrey visual field testing confirmed glaucomatous changes...
June 2018: American Journal of Ophthalmology Case Reports
M K Fehrenbach, U Nestler, J Meixensberger, M K Bernhard, A Merkenschlager, S Weise, M Krause
INTRODUCTION: The ciliopathy "Joubert syndrome" was first described in 1969 by Dr. Marie Joubert and most subtypes follow an autosomal recessive inheritance. The complex disorder shows typical clinical features, such as hyperventilation, abnormal eye movements, and retardation. A pathognomonic midbrain-hindbrain malformation, the molar tooth sign, can be found on magnetic resonance imaging of the brainstem. There are a little more than 200 reports of Joubert syndrome in the literature...
March 5, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Jacelyn Emily Peabody, Ren-Jay Shei, Brent M Bermingham, Scott Edward Phillips, Brett Turner, Steven M Rowe, George Martin Solomon
The respiratory tract is lined with multi-ciliated epithelial cells that function to move mucus and trapped particles via the mucociliary transport apparatus. Genetic and acquired ciliopathies result in diminished mucociliary clearance, contributing to disease pathogenesis. Recent innovations in imaging technology has advanced our understanding of ciliary motion in health and disease states. Application of imaging modalities including transmission electron microscopy (TEM), high-speed video microscopy (HSVM), and micron-optical coherence tomography (μOCT) could improve diagnostics and be applied for precision medicine...
March 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Elizabeth Forsythe, Joanna Kenny, Chiara Bacchelli, Philip L Beales
Bardet-Biedl syndrome is a rare autosomal recessive multisystem disorder caused by defects in genes encoding for proteins that localize to the primary cilium/basal body complex. Twenty-one disease-causing genes have been identified to date. It is one of the most well-studied conditions in the family of diseases caused by defective cilia collectively known as ciliopathies. In this review, we provide an update on diagnostic developments, clinical features, and progress in the management of Bardet-Biedl syndrome...
2018: Frontiers in Pediatrics
Gabrielle Wheway, Liliya Nazlamova, John T Hancock
The presence of single, non-motile "primary" cilia on the surface of epithelial cells has been well described since the 1960s. However, for decades these organelles were believed to be vestigial, with no remaining function, having lost their motility. It wasn't until 2003, with the discovery that proteins responsible for transport along the primary cilium are essential for hedgehog signaling in mice, that the fundamental importance of primary cilia in signal transduction was realized. Little more than a decade later, it is now clear that the vast majority of signaling pathways in vertebrates function through the primary cilium...
2018: Frontiers in Cell and Developmental Biology
Kousuke Kasahara, Hiromasa Aoki, Tohru Kiyono, Shujie Wang, Harumi Kagiwada, Mizuki Yuge, Toshio Tanaka, Yuhei Nishimura, Akira Mizoguchi, Naoki Goshima, Masaki Inagaki
Ciliogenesis is generally inhibited in dividing cells, however, it has been unclear which signaling cascades regulate the phenomenon. Here, we report that epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells. These phosphorylations elevate the deubiquitinase activity, which then stabilizes the trichoplein-Aurora A pathway, an inhibitory mechanism of ciliogenesis. EGFR knockdown and serum starvation result in ciliogenesis through downregulation of the USP8-trichoplein-Aurora A signal...
February 22, 2018: Nature Communications
Éva Sipos, Sámuel Komoly, Péter Ács
Primary cilia are small, special cellular organelles that provide important sensory and signaling functions during the development of mammalian organs and coordination of postnatal cellular processes. Dysfunction of primary cilia are thought to be the main cause of ciliopathies, a group of genetic disorders characterized by overlapping developmental defects and prominent neurodevelopmental features. Although, disrupted cilia-linked signaling pathways have been implicated in the regulation of numerous neuronal functions, the precise role of primary cilia in the brain are still unknown...
February 20, 2018: Journal of Molecular Neuroscience: MN
David K Breslow, Sascha Hoogendoorn, Adam R Kopp, David W Morgens, Brandon K Vu, Margaret C Kennedy, Kyuho Han, Amy Li, Gaelen T Hess, Michael C Bassik, James K Chen, Maxence V Nachury
Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ-tubulin and ε-tubulin and is required for centriole maintenance...
February 19, 2018: Nature Genetics
Katie Weihbrecht, Wesley A Goar, Thomas Pak, Janelle E Garrison, Adam P DeLuca, Edwin M Stone, Todd E Scheetz, Val C Sheffield
Upwards of 90% of individuals with Bardet-Biedl syndrome (BBS) display rod-cone dystrophy with early macular involvement. BBS is an autosomal recessive, genetically heterogeneous, pleiotropic ciliopathy for which 21 causative genes have been discovered to date. In addition to retinal degeneration, the cardinal features of BBS include obesity, cognitive impairment, renal anomalies, polydactyly, and hypogonadism. Here, we review the genes, proteins, and protein complexes involved in BBS and the BBS model organisms available for the study of retinal degeneration...
September 2017: Medical Research Archives
Yun J Sung, Thomas W Winkler, Lisa de Las Fuentes, Amy R Bentley, Michael R Brown, Aldi T Kraja, Karen Schwander, Ioanna Ntalla, Xiuqing Guo, Nora Franceschini, Yingchang Lu, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jonathan Marten, Solomon K Musani, Changwei Li, Mary F Feitosa, Tuomas O Kilpeläinen, Melissa A Richard, Raymond Noordam, Stella Aslibekyan, Hugues Aschard, Traci M Bartz, Rajkumar Dorajoo, Yongmei Liu, Alisa K Manning, Tuomo Rankinen, Albert Vernon Smith, Salman M Tajuddin, Bamidele O Tayo, Helen R Warren, Wei Zhao, Yanhua Zhou, Nana Matoba, Tamar Sofer, Maris Alver, Marzyeh Amini, Mathilde Boissel, Jin Fang Chai, Xu Chen, Jasmin Divers, Ilaria Gandin, Chuan Gao, Franco Giulianini, Anuj Goel, Sarah E Harris, Fernando Pires Hartwig, Andrea R V R Horimoto, Fang-Chi Hsu, Anne U Jackson, Mika Kähönen, Anuradhani Kasturiratne, Brigitte Kühnel, Karin Leander, Wen-Jane Lee, Keng-Hung Lin, Jian 'an Luan, Colin A McKenzie, He Meian, Christopher P Nelson, Rainer Rauramaa, Nicole Schupf, Robert A Scott, Wayne H H Sheu, Alena Stančáková, Fumihiko Takeuchi, Peter J van der Most, Tibor V Varga, Heming Wang, Yajuan Wang, Erin B Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Weihua Zhang, Jing Hua Zhao, Saima Afaq, Tamuno Alfred, Najaf Amin, Dan Arking, Tin Aung, R Graham Barr, Lawrence F Bielak, Eric Boerwinkle, Erwin P Bottinger, Peter S Braund, Jennifer A Brody, Ulrich Broeckel, Claudia P Cabrera, Brian Cade, Yu Caizheng, Archie Campbell, Mickaël Canouil, Aravinda Chakravarti, Ganesh Chauhan, Kaare Christensen, Massimiliano Cocca, Francis S Collins, John M Connell, Renée de Mutsert, H Janaka de Silva, Stephanie Debette, Marcus Dörr, Qing Duan, Charles B Eaton, Georg Ehret, Evangelos Evangelou, Jessica D Faul, Virginia A Fisher, Nita G Forouhi, Oscar H Franco, Yechiel Friedlander, He Gao, Bruna Gigante, Misa Graff, C Charles Gu, Dongfeng Gu, Preeti Gupta, Saskia P Hagenaars, Tamara B Harris, Jiang He, Sami Heikkinen, Chew-Kiat Heng, Makoto Hirata, Albert Hofman, Barbara V Howard, Steven Hunt, Marguerite R Irvin, Yucheng Jia, Roby Joehanes, Anne E Justice, Tomohiro Katsuya, Joel Kaufman, Nicola D Kerrison, Chiea Chuen Khor, Woon-Puay Koh, Heikki A Koistinen, Pirjo Komulainen, Charles Kooperberg, Jose E Krieger, Michiaki Kubo, Johanna Kuusisto, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Benjamin Lehne, Cora E Lewis, Yize Li, Sing Hui Lim, Shiow Lin, Ching-Ti Liu, Jianjun Liu, Jingmin Liu, Kiang Liu, Yeheng Liu, Marie Loh, Kurt K Lohman, Jirong Long, Tin Louie, Reedik Mägi, Anubha Mahajan, Thomas Meitinger, Andres Metspalu, Lili Milani, Yukihide Momozawa, Andrew P Morris, Thomas H Mosley, Peter Munson, Alison D Murray, Mike A Nalls, Ubaydah Nasri, Jill M Norris, Kari North, Adesola Ogunniyi, Sandosh Padmanabhan, Walter R Palmas, Nicholette D Palmer, James S Pankow, Nancy L Pedersen, Annette Peters, Patricia A Peyser, Ozren Polasek, Olli T Raitakari, Frida Renström, Treva K Rice, Paul M Ridker, Antonietta Robino, Jennifer G Robinson, Lynda M Rose, Igor Rudan, Charumathi Sabanayagam, Babatunde L Salako, Kevin Sandow, Carsten O Schmidt, Pamela J Schreiner, William R Scott, Sudha Seshadri, Peter Sever, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, John M Starr, Konstantin Strauch, Hua Tang, Kent D Taylor, Yik Ying Teo, Yih Chung Tham, André G Uitterlinden, Melanie Waldenberger, Lihua Wang, Ya X Wang, Wen Bin Wei, Christine Williams, Gregory Wilson, Mary K Wojczynski, Jie Yao, Jian-Min Yuan, Alan B Zonderman, Diane M Becker, Michael Boehnke, Donald W Bowden, John C Chambers, Yii-Der Ida Chen, Ulf de Faire, Ian J Deary, Tõnu Esko, Martin Farrall, Terrence Forrester, Paul W Franks, Barry I Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Bernardo Lessa Horta, Yi-Jen Hung, Jost B Jonas, Norihiro Kato, Jaspal S Kooner, Markku Laakso, Terho Lehtimäki, Kae-Woei Liang, Patrik K E Magnusson, Anne B Newman, Albertine J Oldehinkel, Alexandre C Pereira, Susan Redline, Rainer Rettig, Nilesh J Samani, James Scott, Xiao-Ou Shu, Pim van der Harst, Lynne E Wagenknecht, Nicholas J Wareham, Hugh Watkins, David R Weir, Ananda R Wickremasinghe, Tangchun Wu, Wei Zheng, Yoichiro Kamatani, Cathy C Laurie, Claude Bouchard, Richard S Cooper, Michele K Evans, Vilmundur Gudnason, Sharon L R Kardia, Stephen B Kritchevsky, Daniel Levy, Jeff R O'Connell, Bruce M Psaty, Rob M van Dam, Mario Sims, Donna K Arnett, Dennis O Mook-Kanamori, Tanika N Kelly, Ervin R Fox, Caroline Hayward, Myriam Fornage, Charles N Rotimi, Michael A Province, Cornelia M van Duijn, E Shyong Tai, Tien Yin Wong, Ruth J F Loos, Alex P Reiner, Jerome I Rotter, Xiaofeng Zhu, Laura J Bierut, W James Gauderman, Mark J Caulfield, Paul Elliott, Kenneth Rice, Patricia B Munroe, Alanna C Morrison, L Adrienne Cupples, Dabeeru C Rao, Daniel I Chasman
Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries...
March 1, 2018: American Journal of Human Genetics
A-L Bruel, J Levy, N Elenga, A Defo, A Favre, H Lucron, Y Capri, L Perrin, S Passemard, Y Vial, A-C Tabet, L Faivre, C Thauvin-Robinet, A Verloes
Oral-facial-digital (OFD) syndromes are a subgroup of ciliopathies distinguished by the co-occurrence of hamartomas and/or multiple frenula of the oral region and digital anomalies. Several clinical forms of OFD are distinguished by their associated anomalies and/or inheritance patterns, and at least 20 genetic types of OFD have been delineated. We describe here a child with preaxial and postaxial polydactyly, lingual hamartoma, a congenital heart defect, delayed development and cerebellar peduncles displaying the molar tooth sign...
February 16, 2018: Clinical Genetics
Rossina Novas, Magdalena Cardenas-Rodriguez, Paola Lepanto, Matías Fabregat, Magela Rodao, María Inés Fariello, Mauricio Ramos, Camila Davison, Gabriela Casanova, Lucía Alfaya, Federico Lecumberry, Gualberto González-Sapienza, Florencia Irigoín, Jose L Badano
Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B is a BBS-associated protein that we have previously shown plays a role in cilia length regulation whereby its depletion results in shortened cilia both in cells and Danio rerio (zebrafish). At least part of that role is achieved by its interaction with the mTORC2 component SIN1, but the mechanistic details of this interaction and/or additional functions that CCDC28B might play in the context of cilia remain poorly understood...
February 14, 2018: Scientific Reports
Katie Weihbrecht, Wesley A Goar, Calvin S Carter, Val C Sheffield, Seongjin Seo
Nephronophthisis-related ciliopathies (NPHP-RC) are a group of disorders that present with end-stage renal failure in childhood/adolescence, kidney cysts, retinal degeneration, and cerebellar hypoplasia. One disorder that shares clinical features with NPHP-RC is Bardet-Biedl Syndrome (BBS). Serologically defined colon cancer antigen 8 (SDCCAG8; also known as NPHP10 and BBS16) is an NPHP gene that is also associated with BBS. To better understand the patho-mechanisms of NPHP and BBS caused by loss of SDCCAG8 function, we characterized an SDCCAG8 mouse model (Sdccag8Tn(sb-Tyr)2161B...
2018: PloS One
Davide Zabeo, John M Heumann, Cindi L Schwartz, Azusa Suzuki-Shinjo, Garry Morgan, Per O Widlund, Johanna L Höög
Eukaryotic flagella are complex cellular extensions involved in many human diseases gathered under the term ciliopathies. Currently, detailed insights on flagellar structure come mostly from studies on protists. Here, cryo-electron tomography (cryo-ET) was performed on intact human spermatozoon tails and showed a variable number of microtubules in the singlet region (inside the end-piece). Inside the microtubule plus end, a novel left-handed interrupted helix which extends several micrometers was discovered...
February 9, 2018: Scientific Reports
Ashwani Sharma, Samuel F Gerard, Natacha Olieric, Michel O Steinmetz
Centrioles are microtubule-based structures that play essential roles in cell division and cilia biogenesis. Cep120 is an important protein for correct centriole formation and mutations in the Cep120 gene cause severe human diseases like Joubert syndrome and complex ciliopathies. Here, we show that Cep120 contains three consecutive C2 domains that are followed by a coiled-coil dimerization domain. Surprisingly, unlike the classical C2 domains, all three Cep120 C2 domains lack calcium- and phospholipid-binding activities...
February 1, 2018: Journal of Structural Biology
Irene Ojeda Naharros, Flavia B Cristian, Jingjing Zang, Matthias Gesemann, Philip W Ingham, Stephan C F Neuhauss, Ruxandra Bachmann-Gagescu
Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous microtubule-based organelles involved in signal transduction. Cilia are anchored inside the cell through basal bodies (BBs), modified centrioles also acting as microtubule-organization centers. Photoreceptors (PRs) are sensory neurons, whose primary cilium forms a highly specialized compartment called the outer segment (OS) responsible for sensing incoming light. Thus, ciliopathies often present with retinal degeneration. Mutations in KIAA0586/TALPID3 (TA3) cause Joubert syndrome, in which 30% of affected individuals develop retinal involvement...
February 2, 2018: Scientific Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"